The Journal of Organic Chemistry
136.8, 132.4, 131.6, 130.1, 129.8, 127.6, 127.4 (d, JC−F = 8.7
Article
3
1′-Methyl-2-(quinolin-8-yl)-6-(trifluoromethyl)spiro[isoindoline-
1,3′-pyrrolidine]-2′,3,5′-trione (3h).
Hz), 126.9, 122.2, 117.8 (d, 2JC−F = 22.5 Hz), 108.1 (d, 2JC−F
=
25 Hz), 71.0, 37.6, 25.9. HRMS (ESI) m/z: calcd for
C21H15FN3O3 [M + H]+, 376.1097; found, 376.1096.
6-Chloro-1′-methyl-2-(quinolin-8-yl)spiro[isoindoline-1,3′-pyrro-
lidine]-2′,3,5′-trione (3e).
White solid, mp 246−248 °C, hexane/EtOAc (50/50), 89%
(95 mg). 1H NMR (500 MHz, CDCl3): δ 8.84 (d, J = 1.1 Hz,
1H), 8.23 (d, J = 8.3 Hz, 1H), 8.15 (d, J = 7.7 Hz, 1H), 7.92
(dd, J = 18.8, 8.0 Hz, 2H), 7.80 (d, J = 7.2 Hz, 1H), 7.66−7.58
(m, 2H), 7.45 (dd, J = 8.1, 4.0 Hz, 1H), 3.42 (d, J = 19.2 Hz,
1H), 3.21 (d, J = 19.1 Hz, 1H), 3.08 (s, 3H).·13C{1H} NMR
(126 MHz, CDCl3): δ 174.3, 173.3, 167.3, 151.4, 145.1, 144.9,
White solid, mp 260−262 °C, hexane/EtOAc (50/50), 90%
(88 mg). 1H NMR (600 MHz, CDCl3): δ 8.84 (d, J = 3.0 Hz,
1H), 8.22 (d, J = 8.6 Hz, 1H), 7.94 (dd, J = 15.0, 8.2 Hz, 2H),
7.80 (d, J = 7.3 Hz, 1H), 7.61−7.59 (m, 2H), 7.45 (dd, J = 8.2,
3.9 Hz, 1H), 7.35 (s, 1H), 3.37 (d, J = 18.9 Hz, 1H), 3.16 (d, J
= 18.9 Hz, 1H), 3.07 (s, 3H).·13C{1H} NMR (151 MHz,
CDCl3): δ 174.4, 173.5, 167.7, 151.3, 146.1, 145.2, 139.4,
136.8, 132.2, 131.5, 130.6, 130.1, 129.9, 129.7, 126.9, 126.3,
122.2, 121.0, 70.97, 37.5, 25.9. HRMS (ESI) m/z: calcd for
C21H15ClN3O3 [M + H]+, 392.0802; found, 392.0802.
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136.8, 135.0 (q, C−F, JC−F = 32.5 Hz), 134.8, 132.0, 131.4,
130.0, 129.8, 127.4, 126.8, 125.8, 123.5 (q, C−F, 1JC−F = 271.2
Hz), 122.2, 71.3, 60.5, 37.3, 25.9. HRMS (ESI) m/z: calcd for
C22H15F3N3O3 [M + H]+, 426.1066; found, 426.1062.
1′-Methyl-2′,3,5′-trioxo-2-(quinolin-8-yl)spiro[isoindoline-1,3′-
pyrrolidine]-6-carbonitrile (3i).
6-Bromo-1′-methyl-2-(quinolin-8-yl)spiro[isoindoline-1,3′-pyrro-
lidine]-2′,3,5′-trione (3f).
White solid, mp 290−291 °C, hexane/EtOAc (50/50), 76%
(73 mg). 1H NMR (500 MHz, CDCl3): δ 8.84 (dd, J = 4.2, 1.7
Hz, 1H), 8.24 (dd, J = 8.3, 1.6 Hz, 1H), 8.12 (d, J = 7.8 Hz,
1H), 7.96 (dd, J = 8.3, 1.2 Hz, 1H), 7.92 (dd, J = 7.8, 1.2 Hz,
1H), 7.78 (dd, J = 7.4, 1.3 Hz, 1H), 7.72 (s, 1H), 7.65−7.59
(m, 1H), 7.47 (dd, J = 8.3, 4.2 Hz, 1H), 3.40 (d, J = 19.1 Hz,
1H), 3.18 (d, J = 19.1 Hz, 1H), 3.07 (s, 3H).·13C{1H} NMR
(126 MHz, CDCl3): δ 173.9, 173.0, 166.8, 163.3, 151.4, 145.0,
136.8, 135.3, 134.0, 131.8, 131.3, 130.4, 129.7, 126.9, 126.0,
124.6, 122.3, 117.6, 116.5, 71.2, 37.2, 26.0. HRMS (ESI) m/z:
calcd for C22H15N4O3 [M + H]+, 383.1144; found, 383.1131.
White solid, mp 261−262 °C, hexane/EtOAc (50/50), 75%
(82 mg). 1H NMR (500 MHz, CDCl3): δ 8.84 (dd, J = 4.1, 1.3
Hz, 1H), 8.23 (dd, J = 8.3, 1.4 Hz, 1H), 7.93 (d, J = 8.2 Hz,
1H), 7.89 (d, J = 8.1 Hz, 1H), 7.83−7.79 (m, 1H), 7.76 (dd, J
= 8.1, 1.0 Hz, 1H), 7.62−7.59 (m, 1H), 7.52−7.49 (m, 1H),
7.45 (dd, J = 8.3, 4.2 Hz, 1H), 3.37 (d, J = 19.1 Hz, 1H), 3.16
(d, J = 19.1 Hz, 1H), 3.08 (s, 3H).·13C{1H} NMR (126 MHz,
CDCl3): δ 174.5, 173.5, 167.8, 151.3, 146.2, 145.2, 136.8,
133.5, 132.3, 131.6, 130.4, 130.1, 129.8, 127.7, 126.9, 126.5,
123.9, 122.2, 71.0, 37.5, 25.9. HRMS (ESI) m/z: calcd for
C21H14KBrN3O3 [M + K]+, 473.9856; found, 473.9842.
1′-Methyl-2′,3,5′-trioxo-2-(quinolin-8-yl)spiro[isoindoline-1,3′-
pyrrolidine]-6-carbaldehyde (3j).
6-Iodo-1′-methyl-2-(quinolin-8-yl)spiro[isoindoline-1,3′-pyrroli-
dine]-2′,3,5′-trione (3g).
White solid, mp 289−290 °C, hexane/EtOAc (50/50), 77%
(93 mg). 1H NMR (500 MHz, CDCl3): δ 8.84 (d, J = 4.1 Hz,
1H), 8.23 (d, J = 8.3 Hz, 1H), 7.95 (dd, J = 19.6, 8.1 Hz, 2H),
7.80 (d, J = 7.3 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.71 (s,
1H), 7.62−7.59 (m, 1H), 7.45 (dd, J = 8.3, 4.2 Hz, 1H), 3.36
(d, J = 19.1 Hz, 1H), 3.15 (d, J = 19.1 Hz, 1H), 3.08 (s,
3H).·13C{1H} NMR (126 MHz, CDCl3): δ 174.5, 173.6,
168.1, 151.3, 146.2, 145.2, 139.4, 136.8, 132.2, 131.6, 131.0,
130.1, 129.8, 129.7, 126.9, 126.5, 122.2, 99.8, 70.8, 37.5, 25.9.
HRMS (ESI) m/z: calcd for C21H15IN3O3 [M + H]+,
484.0158; found, 484.0143.
White solid, mp 297−298 °C, hexane/EtOAc (50/50), 69%
1
(67 mg). H NMR (500 MHz, CDCl3): δ 10.15 (s, 1H), 8.86
(dd, J = 4.1, 1.5 Hz, 1H), 8.25 (dd, J = 8.3, 1.4 Hz, 1H), 8.21
(d, J = 7.7 Hz, 1H), 8.14 (d, J = 7.7 Hz, 1H), 7.97 (d, J = 7.7
Hz, 1H), 7.91 (s, 1H), 7.82 (d, J = 7.2 Hz, 1H), 7.65−7.61 (m,
1H), 7.48 (dd, J = 8.3, 4.2 Hz, 1H), 3.42 (d, J = 19.1 Hz, 1H),
3.21 (d, J = 19.1 Hz, 1H), 3.10 (s, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 191.1, 174.4, 173.4, 167.5, 151.4, 145.2,
145.2, 139.9, 136.9, 136.5, 132.8, 132.2, 131.5, 130.4, 129.8,
127.0, 126.0, 122.3, 120.4, 71.4, 37.4, 26.0. HRMS (ESI) m/z:
calcd for C22H16N3O4 [M + H]+, 386.1141; found, 386.1120.
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J. Org. Chem. XXXX, XXX, XXX−XXX